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Regioselective synthesis of 6-amino- and 6-amido-6-deoxypullulans

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Abstract

Hydrophobically modified polysaccharides that contain amine and amide groups possess valuable features for drug delivery and other applications. These chemical groups are known to play a fundamental role in the biological activity of important polysaccharides. Pullulan is known for its non-toxicity and biocompatibility, therefore, we have applied the versatile Staudinger reaction for the synthesis of regioselectively substituted pullulan derivatives containing amine or amide groups with promise for biomedical applications. The synthesis began with the regioselective bromination of pullulan at C-6 with N-bromosuccinimide and triphenylphosphine, providing 6-bromo-6-deoxy-pullulan, which is soluble in a range of organic solvents and therefore is a dynamic intermediate for the synthesis of other pullulan derivatives. Azide displacement of bromide from 6-bromo-6-deoxy-pullulan esters yielded the corresponding 6-azido-6-deoxy-pullulan esters. Staudinger reduction of these azides efficiently and chemoselectively afforded the corresponding amino- or amidopullulans.

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Acknowledgments

We thank Hayashibara Company for their kind donation of pullulan. We thank the Macromolecules and Interfaces Institute (MII) at Virginia Tech for providing a doctoral fellowship to JP and the Institute for Critical Technologies and Applied Science (ICTAS) at Virginia Tech for facilities support. We also thank the National Science Foundation for their help in financing this project through Grant Numbers DMR-0804501 and DMR-1308276. We are grateful for the help of Michelle Mahoney in the optimization of the bromination reaction and also to Mark Flynn and Sue Mecham for running and help interpreting the SEC data. For the SEC used in this work, the authors greatly acknowledge financial support by the National Science Foundation under the Grant Number DMR-1126534.

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  1. Macromolecules and Interfaces Institute, Virginia Tech, 240 ICTAS, Blacksburg, VA, 24061, USA

    Junia M. Pereira & Kevin J. Edgar

  2. Department of Sustainable Biomaterials, Virginia Tech, 230 Cheatham Hall, Blacksburg, VA, 24061, USA

    Kevin J. Edgar

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  1. Junia M. Pereira
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Correspondence to Kevin J. Edgar.

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Pereira, J.M., Edgar, K.J. Regioselective synthesis of 6-amino- and 6-amido-6-deoxypullulans. Cellulose 21, 2379–2396 (2014). https://doi.org/10.1007/s10570-014-0259-6

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